Relapse remains the most important cause of failure for many patients undergoing either autologous or allogeneic[unreadable] transplant for the treatment of malignant lymphoma and acute myelogenous leukemia. This project will focus on studies[unreadable] of radioimmunotherapy targeted to tumor-associated antigens, as a component of the preparatory regimens for[unreadable] autologous and allogeneic hematopoietic cell transplantation used in the treatment of these diseases. The proposed[unreadable] studies seek to improve the anti-tumor efficacy, as well as reduce the toxicity of the procedure which will extend the[unreadable] application of hematopoietic cell transplantation (HCT) to older patients who form the majority of patients with both AML[unreadable] and lymphoma. The proposed studies will investigate the incorporation of radiolabeled antibodies conjugated to a[unreadable] heavy metal radioisotope (Yttrium-90) that target either the CD20 antigen on malignant B-cells or the CD33 antigen on[unreadable] blasts in patients with AML and myelodysplasia. We propose to perform five clinical studies using novel regimens for[unreadable] autologous or allogeneic transplant for AML and B-cell lymphoma: 1) For patients with advanced lymphoma (low-grade,[unreadable] intermediate-grade, and mantle cell) we will continue our studies of high-dose 90Y-labeled anti-CD20 antibody combined[unreadable] with etoposide and cyclophosphamide in the Phase II setting; 2) For older patients (age>60) with relapsed lymphoma[unreadable] we will extend our Phase I observations to a Phase II study of 90Y-labeled anti-CD20 antibody combined with BEAM[unreadable] chemotherapy in order to develop an effective regimen that can be used safely in this population of patients;[unreadable] 3) 90Y-labeled anti-CD20 antibody will also be developed as part of a reduced intensity allogeneic transplant regimen for patients with lymphoma who are not candidates for an autologous approach, including those with relapsed mantle cell lymphoma, multiple relapsed low-grade lymphoma, or patients who have relapsed after autologous transplant; 4) For patients with AML, who have intermediate- and high-risk cytogenetics, we will initiate a study of 90Y-labeled anti-CD33 antibody to replace total body irradiation in combination with etoposide and cyclophosphamide for autologous[unreadable] transplant; 5) After completion of a Phase I safety study, we will conduct a Phase II study with this regimen. For[unreadable] patients with advanced leukemia (early relapse, older age, AML with prior MDS, relapse after auto-transplant), we will[unreadable] incorporate the 90Y-labeled anti-CD33 antibody into a reduced intensity allogeneic transplant regimen to improve the[unreadable] outcome for this high-risk population of patients. It is the general hypothesis of this project that targeted radiation[unreadable] therapy as a component of the autologous and allogeneic transplant preparative regimens will help improve therapeutic[unreadable] efficacy by decreasing post-HCT disease relapse and by reducing toxicity, thereby extending the potential benefit of[unreadable] treatment to a larger population of patients with these diseases.